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Biodistribution of long-circulating PEG-grafted nanocapsules in mice: effects of PEG chain length and density.
Mosqueira, V C; Legrand, P; Morgat, J L; Vert, M; Mysiakine, E; Gref, R; Devissaguet, J P; Barratt, G.
Afiliación
  • Mosqueira VC; UMR CNRS 8612, Faculté de Pharmacie, Université de Paris-Sud, Châtenay Malabry, France.
Pharm Res ; 18(10): 1411-9, 2001 Oct.
Article en En | MEDLINE | ID: mdl-11697466
PURPOSE: To study the pharmacokinetics and biodistribution of novel polyethyleneglycol (PEG) surface-modified poly(rac-lactide) (PLA) nanocapsules (NCs) and to investigate the influence of PEG chain length and content. METHODS: The biodistribution and plasma clearance in mice of different NC formulations were studied with [3H]-PLA. PLA-PEG copolymers were used in NC preparations at different chain lengths (5 kDa and 20 kDa) and PEG contents (10% and 30% w/w of total polymer). In vitro and in vivo stability were also checked. RESULTS: Limited [3H]-PLA degradation was observed after incubation in mouse plasma for 1 h, probably because of to the large surface area and thin polymer wall. After injection into mice. NCs prepared with PLA-PEG copolymers showed an altered distribution compared to poloxamer-coated PLA NCs. An increased concentration in plasma was also observed for PLA-PEG NCs. even after 24 h. A dramatic difference in the pharmacokinetic parameters of PLA-PEG 45-20 30% NCs compared to poloxamer-coated NCs indicates that covalent attachment, longer PEG chain lengths, and higher densities are necessary to produce an increased half-life of NCs in vivo. CONCLUSIONS: Covalently attached PEG on the surface of NCs substantially can reduce their clearance from the blood compartment and alter their biodistribution.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polietilenglicoles / Cápsulas / Nanotecnología Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Pharm Res Año: 2001 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polietilenglicoles / Cápsulas / Nanotecnología Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Pharm Res Año: 2001 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos